DESCRIPTION: (Applicant's Description) Cigarette smoking is the leading preventable cause of cancer and cardiovascular diseases. Although the decades have witnessed accelerated efforts to develop effective smoking cessation strategies, the long-term success rates have been disappointing. The majority of smokers relapse within two weeks of a cessation attempt, and little is known about the nature of this early relapse. Smoking cessation is associated with negative affect symptoms. These symptoms are intensified in stressful situations, possibly accelerating the progression towards a full relapse. Mechanisms responsible for this stress effect are not known. Without specific knowledge of the stress-related biobehavioral changes, targeted efforts to reduce smoking and relapse will remain limited. The long-term goal of this research is to determine the psycho biological mechanisms responsible for smoking relapse. The specific goal of this project is to evaluate hormonal changes during early abstinence and in response to behavioral stress, and to assess the extent to which these changes predict early relapse. Our central hypothesis is that exaggerated responses to behavioral stress predict a shorter time to relapse. This hypothesis is based on the well-established observation that stressful events, characterized by negative emotions, are associated with rises in adrenocorticotropic hormone (ACTH) and cortisol concentrations. It is also based on the observation that environmental stressors increase the risk for smoking relapse. We will specifically determine the extent to which basal cortisol activity during early smoking abstinence predicts relapse, examine endocrine and cardiovascular responses to stress as predictors of smoking relapse, and evaluate gender differences in psycho biological changes during smoking abstinence and in response to behavioral stress. This research focuses on the pituitary-adrenocortical axis, an important stress-related biological system recently implicated in addiction. We will integrate hormonal, autonomic and psychological indices to gain an accurate profile of the stress response patterning among smokers and use this information in a prospective fashion to predict relapse in men and women. The results will provide a base of knowledge concerning psycho biological changes associated with quitting and risk for relapse. This information will facilitate efforts towards improving methods to identify and assist individuals at high risk for relapse. Reducing relapse rates will contribute significantly towards reducing smoking and its harmful effects.